December 20, 2007

Researcher Seeks to Stop Respiratory ‘Vicious Cycle’ in DMD

MDA grantee Tejvir S. Khurana at the University of Pennsylvania and colleagues say they’ve found support for their hypothesis that low levels of oxygen (hypoxia) not only result from impaired respiratory muscle function in Duchenne muscular dystrophy (DMD), but that a lack of sufficient oxygen also causes further damage to the respiratory and other muscles. If this hypothesis proves to be true, Khurana says, weakened respiratory muscles would cause hypoxia, which would cause more muscle weakness, setting up a vicious cycle.

His research group is conducting experiments in mice, worms and flies that lack the dystrophin protein and therefore have a DMD-like disease.

Khurana, with German medical student Gabriel Willmann, recently conducted some of the experiments on Mount McKinley in Alaska, which is about 20,000 feet above sea level and provides a very low-oxygen environment. The environment, while potentially dangerous for the researchers, allowed them to accurately mimic the effects of impaired respiration seen in DMD, Khurana says. (MDA didn’t fund the Mount McKinley expedition.)

Next, the investigators want to try to stabilize a protein called hypoxia-inducible factor (HIF), which can help an organism to compensate for hypoxia but which is normally degraded quickly. HIF’s actions include coaxing the formation of new blood vessels, increasing production of red blood cells and changing metabolism. Khurana says he hopes stabilizing HIF might provide a new treatment for MD-induced hypoxia.